The explosion was heard on Sunday night from inside the Al Tanf base which hosts US occupation forces.
The cause of the incident is unknown and there were no immediate reports of possible damage or casualties.
CENTCOM has not commented on this issue so far.
The al-Tanf base is located in the Homs province of Syria, near the borders of Iraq and Jordan.
Earlier on Sunday, several explosions were heard at the US base in Syria's Al-Omar oil field.
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